Transformation malignant

Nucleic acids in the DNA contain a high number of nucleophilic sites that can be attacked by electrophilic intermediates (metabolites) of chemical compounds. DNA adducts formed may cause alterations in the expression of a critical gene in the cell and thus lead to cell death. For example, modification of p53 tumor suppressor gene may inactivate the functions of the p53 protein and render cells sensitive to malignant transformation. Also, formation of RNA adducts may inhibit key cellular events because RNA is essential for protein synthesis. 

BCR-ABL tyrosine kinase that is essential for malignant transformation. Cytogenetic responses to IFN-a therapy were seen in 30-40% of the treated patients with complete responses in about 10%. Long term survival can therefore be expected in these patients. In 2000, the BCR-ABL tyrosine kinase inhibitor Imatinib has been introduced for CML therapy and meanwhile has proven more efficient than IFN-a therapy. 

Some established cell lines were derived from malignant tissue. Many of these cell lines can form tumors when injected into susceptible animals. Other established cell lines are not Uunorigenic. However, exposure to carcinogens, and irradiation can cause these cells to form tumors in susceptible animals. In addition, transformation can be caused by spontaneous mutations, by growth factors, and by viral (or oncogenic) transformation (Table 6). Malignant transformation is defined as consisting of the series of events that cause normal cells to develop the capacity to form tumors. 

Figure 12. An alteration in a signal transduction pathway may be associated with malignant transformation.

Virally induced antigens result from a malignant transformation occurring in the cell, due to an oncogenic vims. These evoke powerful immune responses in experimental animals. 

Singh, V.S. and Gaby, S.K. (1991). Premalignant lesions role of antioxidant vitamins and /3-carotene in risk reduction and prevention of malignant transformation. Am. J. Clin. Nutr. 53, 386S-390S. 

Weitzman, S.A., Weitberg, A.B., Clark, E.P., Clark, T.P. and Stossel, T.P. (1985). Phagocytes as carcinogens malignant transformation produced by human neutrophils. Science 227, 1231-1233. 

Familial adenomatous polyposis An inherited condition in which numerous polyps form, mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs 100% of the time when not treated. 

Krinsky, N. 1993. Micronutrients and their influence on mutagenicity and malignant transformation. Ann N Y Acad Sci 28 229-242. Review. 

Lazaris-Karatzas, A., Montine, K. S., and Sonenberg, N. (1990). Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA S cap. Nature 345, 544-547. 

Current lung dosimetry models are based on the assumption that basal cells of the bronchial epithelium are the critical target cells for malignant transformation and that the alpha dose to these cells is the relevant radiation dose. 

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